{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:34:36Z","timestamp":1791056076822,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>IL8RA and IL8RB, encoded by <jats:italic>CXCR1<\/jats:italic> and <jats:italic>CXCR2<\/jats:italic>, are receptors for interleukin (IL)-8 and other CXC chemokines involved in chemotaxis and activation of polymorphonuclear neutrophils (PMN). Variants at <jats:italic>CXCR1<\/jats:italic> and <jats:italic>CXCR2<\/jats:italic> have been associated with susceptibility to cutaneous and mucocutaneous leishmaniasis in Brazil. Here we investigate the role of <jats:italic>CXCR1\/CXCR2<\/jats:italic> in visceral leishmaniasis (VL) in India.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Three single nucleotide polymorphisms (SNPs) (rs4674259, rs2234671, rs3138060) that tag linkage disequilibrium blocks across <jats:italic>CXCR1\/CXCR2<\/jats:italic> were genotyped in primary family-based (313 cases; 176 nuclear families; 836 individuals) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between <jats:italic>CXCR1\/CXCR2<\/jats:italic> variants and VL. Quantitative RT\/PCR was used to compare CXCR1\/CXCR2 expression in mRNA from paired splenic aspirates taken before and after treatment from 19 VL patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Family-based analysis using FBAT showed association between VL and SNPs <jats:italic>CXCR1<\/jats:italic>_rs2234671 (Z-score = 2.935, <jats:italic>P<\/jats:italic> = 0.003) and <jats:italic>CXCR1<\/jats:italic>_rs3138060 (Z-score = 2.22, <jats:italic>P<\/jats:italic> = 0.026), but not with <jats:italic>CXCR2<\/jats:italic>_rs4674259. Logistic regression analysis of the case-control data under an additive model of inheritance showed association between VL and SNPs <jats:italic>CXCR2<\/jats:italic>_rs4674259 (OR = 1.15, 95%CI = 1.01-1.31, <jats:italic>P<\/jats:italic> = 0.027) and <jats:italic>CXCR1<\/jats:italic>_rs3138060 (OR = 1.25, 95%CI = 1.02-1.53, <jats:italic>P<\/jats:italic> = 0.028), but not with <jats:italic>CXCR1<\/jats:italic>_rs2234671. The 3-locus haplotype T_G_C across these SNPs was shown to be the risk haplotype in both family- (TRANSMIT; <jats:italic>P<\/jats:italic> = 0.014) and population- (OR = 1.16, <jats:italic>P<\/jats:italic> = 0.028) samples (combined <jats:italic>P<\/jats:italic> = 0.002). CXCR2, but not CXCR1, expression was down regulated in pre-treatment compared to post-treatment splenic aspirates (<jats:italic>P<\/jats:italic> = 0.021).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This well-powered primary and replication genetic study, together with functional analysis of gene expression, implicate CXCR2 in determining outcome of VL in India.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-12-162","type":"journal-article","created":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T19:18:01Z","timestamp":1323976681000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Genetic and functional evaluation of the role of CXCR1 and CXCR2 in susceptibility to visceral leishmaniasis in north-east India"],"prefix":"10.1186","volume":"12","author":[{"given":"Sanjana","family":"Mehrotra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Fakiola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Oommen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra E","family":"Jamieson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshuman","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhavi","family":"Sudarshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puja","family":"Tiwary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa Selvi","family":"Rani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumarasamy","family":"Thangaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhukar","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenefer M","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,12,15]]},"reference":[{"issue":"3","key":"892_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0035-9203(01)90223-8","volume":"95","author":"P Desjeux","year":"2001","unstructured":"Desjeux P: The increase in risk factors for leishmaniasis worldwide. 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